Beyond Neurons: Oligodendrocyte Dysfunction and Myelin Pathophysiology in Alcohol Use Disorder.

Myelin Alteration in Neurodevelopmental Disorders: Integrating Clinical and Preclinical Evidence.

The evidence suggests that myelin-related pathways represent a common point of vulnerability across disorders and may offer a potential target for intervention, integrating findings from both animal models and human research.

Alcohol-induced structural and cellular brain alterations: molecular and histopathological mechanisms.

Chronic alcohol consumption is a leading cause of acquired neurodegeneration with well-documented structural and ultrastructural brain alterations. This review analyzes the cellular and molecular mechanisms underlying alcohol neurotoxicity, integrating findings from animal models, human post-mortem studies, and neuroimaging investigations. Ethanol crosses the blood-brain barrier and generates toxic metabolites including acetaldehyde and reactive oxygen species, triggering oxidative stress, lipid peroxidation, and mitochondrial dysfunction. Chronic exposure induces glutamatergic and gamma-aminobutyric acid (GABA)ergic adaptations leading to excitotoxicity during withdrawal. Cell death occurs through apoptotic, necrotic, and necroptotic pathways, while microglial and astrocytic activation perpetuates neuroinflammation. Histopathological (HP) changes include selective neuronal loss in the prefrontal cortex, hippocampus, and cerebellum, dendritic simplification, and synaptic alterations. White matter pathology manifests as demyelination and axonal degeneration. Associated thiamine deficiency produces characteristic lesions in the mammillary bodies, thalamus, and cerebellar vermis. Neuroimaging techniques provide valuable HP correlates and biomarkers for disease monitoring. While some changes demonstrate partial reversibility with abstinence through remyelination and synaptic plasticity, extensive neuronal loss remains irreversible. Understanding these mechanisms is essential for developing neuroprotective therapeutic strategies.

Neuroprogression in substance use disorders: Integrating molecular mechanisms, brain circuitry, biomarkers, and implications for clinical staging and service design.

Overall, neuroprogression provides a coherent model for understanding SUDs and may contribute to guiding more precise, biologically informed approaches in addiction psychiatry.

Myelin and Oligodendrocyte Dysfunction in Demyelinating and Neurodegenerative Disorders: Signaling Pathways and Therapeutic Targets.

Myelin integrity and oligodendrocyte function are central to the progression of demyelinating and neurodegenerative diseases and targeting molecular pathways involved in myelination offers significant potential for improving disease outcomes and developing advanced therapeutic strategies.

From Perinatal Stress to Schizophrenia: The Emerging Role of Glial Pathology

Background Glia are the non-excitable cells of the brain, which, upon hyperstimulation, give rise to neuropsychiatric disorders. Recent evidence suggests that they are highly reactive cells, which makes them prone to environmental stimuli and early-life stressors. Upon excessive or chronic stimulation through exposure to stressors, these cells become responsible for causing neurological damage, which leads to neuropsychiatric disorders like schizophrenia, a global burden with no definite interventions. Purpose Perinatal stressors such as protein malnourishment, immunological disturbances, toxins, parental separation and abuse play a major role in negatively changing the cytoarchitecture and homeostasis of both neurons and glial cells (astrocytes, microglia and oligodendrocytes), finally degrading both cognitive and behavioural abilities. Effects of excessive glial activation and/or degeneration result in neuroinflammation, memory loss, anxiety, depression and hyperactivity-like symptoms in adult individuals, which contribute to the manifestation of schizophrenic pathology. Conclusion Therefore, it is believed that perinatal stressor-associated negative changes in glia can predispose an individual to develop this disorder later in life. This review summarises current evidence on how diverse early-life stressors influence glial cells, which could contribute to the neurobiological mechanism underlying schizophrenia.

Enhancing Oligodendrogenesis Rescues Chronic Stress‐Induced Behavioral Disorders Involving Neuronal and Synaptic Reorganization